Bioavailability Comparison of Midazolam Oromucosal Solution Versus Solution for Injection in Healthy Subjects
- Trial ID
- 2023-504903-10-00
- Protocol
- LESVIBUCCO/23/BQ-3
Trial statistics
Objectives
The primary objective of this study is to evaluate the **bioavailability** of Midazolam 7.5 mg/1.5 mL oromucosal solution (Buccolam®) compared to the 10 mg/2 mL solution for injection (Hypnovel®) in healthy subjects. This comparison is clinically relevant as it aims to determine the pharmacokinetic profile of the oromucosal formulation relative to the injectable form, which could inform dosing strategies and administration routes in clinical practice.
Participants
The clinical trial involves a study population that includes both **male** and **female** participants. The age range of the participants spans from **children** to **adolescents**, as indicated by the age range categories provided. The trial population is noted to include a **vulnerable population**, although specific details regarding the nature of this vulnerability are not disclosed. The sponsor has not provided information regarding the total number of participants involved in the study. Participants are not required to have any specific medical condition, as the trial is open to individuals without any pre-existing health issues. Lifestyle considerations such as diet, physical activity, or habits have not been specified in the available data. The selection criteria for the trial population, including any key inclusion or exclusion criteria, have not been detailed by the sponsor.
Plans and Procedures
The clinical trial is designed to evaluate the **bioavailability** of two formulations of **midazolam**: a 7.5 mg/1.5 mL oromucosal solution and a 10 mg/2 mL solution for injection. This study is a Phase 2, randomized, double-blind, controlled trial conducted in healthy subjects. The trial is expected to commence recruitment on July 10, 2023, and conclude by October 31, 2023. Participants will be involved in the study for a duration that aligns with the trial's estimated timeline, with specific involvement periods determined by the study protocol.
The sequence of study visits includes an initial screening visit to assess eligibility based on predefined criteria. Following successful screening, participants will be randomized to receive one of the two formulations. Subsequent follow-up visits will be scheduled to monitor the pharmacokinetic parameters and any adverse events. The end-of-study visit will occur after the final dose administration and will include a comprehensive evaluation of the participant's health status and study outcomes.
Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial's design ensures that all data collected will contribute to understanding the comparative bioavailability of the two midazolam formulations, with the aim of optimizing therapeutic strategies in clinical practice.
Treatment
The clinical trial involves the administration of an **experimental medication**. However, specific details regarding the name, pharmaceutical form, dosage, route, and frequency of administration of the experimental medication are not provided in the available data. The trial documentation does not specify whether the medication is a **paediatric formulation** or if it is classified as an **orphan drug**. Additionally, there is no information on the maximum daily dose, total dose, or treatment period for the experimental medication.
In this study, there is no mention of any **non-experimental treatments** such as standard-of-care therapy, placebo, or comparator treatment being used. The data does not provide details on any additional relevant information about drug administration, dosing schedules, or participant compliance monitoring. The absence of these details suggests that the trial documentation may be incomplete or that such information is not applicable to this particular study.
Efficacy
The clinical trial is in Phase 2 and is scheduled to have an estimated recruitment start date of July 10, 2023, with an estimated end date of October 31, 2023. Efficacy will be assessed through the evaluation of primary and secondary endpoints, although specific endpoints are not detailed in the provided data. The trial will follow a structured schedule for measuring and collecting efficacy parameters, adhering to standard clinical trial protocols. The analysis of these parameters will be conducted using scientifically validated methods appropriate for a Phase 2 trial. The trial's design and execution will ensure that efficacy assessments are objective and reliable, contributing to the overall evaluation of the investigational product's therapeutic potential.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Free written informed consent prior to any procedure required by the study.
- Male or female subject ≥18 years at the time of signing the informed consent.
- Body mass index (BMI) of 18.5 to 35.0 kg/m2, inclusive, and body weight ≥50 kg.
- No clinically relevant diseases captured in medical history.
- No clinically relevant abnormalities on physical examination.
- No clinically relevant abnormalities on vital signs.
- No clinically relevant abnormalities on 12-lead ECG.
- No clinically relevant abnormalities on clinical laboratory tests.
- Negative test results for anti-Human Immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus antibodies (anti-HCVAb).
- Non-smoker or ex-smoker (i.e., someone who abstained from using tobacco- or nicotine-containing products for at least 3 months prior to Screening).
- Willingness to accept and comply with all study procedures and restrictions.
- A female subject is eligible if she meets one of the following criteria: a) is of non-childbearing potential; or b) is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to admission to the first study period until the end of study.
Exclusion Criteria
- Known hypersensitivity / allergy reaction to the study drug substance or any of the excipients.
- Known severe hypersensitivity reaction to any other drug.
- Any medical condition (e.g., gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (e.g., cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
- History of cardiovascular or respiratory disease.
- History of renal or hepatic impairment.
- History of severe respiratory insufficiency.
- History of sleep apnea syndrome.
- History of myasthenia gravis.
- Current or recurrent abnormality in the oral cavity/mucosa.
- Difficult airway, congenital mouth and tongue enlargement, and mandibular dysplasia.
- History of alcohol or drug abuse.
- Serum transaminases ALT or AST above the upper limit of the normal range.
- Estimated renal creatinine clearance (CLCR) below the lower limit of normal range (i.e., 90-120 mL/min/1.73 m2 for males and 80-110 mL/min/1.73 m2 for females) for subjects with age up to 59 years, or below 80 mL/min/1.73 m2 for males and below 70 mL/min/1.73 m2 for females with age of 60 years or above, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average surface area of 1.73 m2.
- Positive result in drugs-of-abuse or ethanol tests.
- Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months.
- Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
- Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
- Participation in any clinical trial within the previous 2 months.
- Participation in more than 2 clinical trials within the previous 12 months.
- Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
- Difficulty in fasting or any dietary restriction such as lactose intolerance, vegan, low-fat, low sodium, etc., that may interfere with the diet served during the study.
- Veins unsuitable for intravenous puncture on either arm.
- If woman, positive pregnancy test in serum.
- If woman, she is breast-feeding.
- Any other condition that the Investigator considers to render the subject unsuitable for the study.
- Any recent disease or condition or treatment that, according to the Investigator, would put the subject at undue risk due to study participation or occurred at a timeframe in which may interfere with the pharmacokinetics of study drug.
- Use of prescription or nonprescription medicinal products, vitamins, food supplements or herbal supplements (including St John’s Wort) within the previous 2 weeks prior to admission to Period 1 or during the washout period prior to Period 2, unless in the Investigator’s opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
- Use of CYP3A4 or CYP3A5-inhibitor (antiproteases, ketoconazole, itraconazole, erythromycin and clarithromycin) or inducer drugs (e.g., rifampicin, phenobarbital, carbamazepine) within the previous 4 weeks prior to admission to Period 1 or during the washout period prior to Period 2.
- Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous week.
- Positive result in drugs-of-abuse or ethanol tests.
- If woman, positive pregnancy test in urine.
- Any other condition that the investigator considers to render the subject unsuitable for the study period.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Portugal | Not Recruiting | 10 Jul 2023 | 24 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BUCCOLAM 7.5 mg oromucosal solution | Test | OROMUCOSAL SOLUTION | OROMUCOSAL USE | 15 | 1 | PRD8810401 |
Hypnovel | Comparator | SOLUTION FOR INJECTION | INTRAMUSCULAR INJECTION | 10 | 1 | PRD7781040 |